Journal of Medical Virology,
Journal Year:
2024,
Volume and Issue:
97(1)
Published: Dec. 26, 2024
ABSTRACT
The
outbreak
of
clade
II
monkeypox
virus
(MPXV)
and
the
additional
in
Central
Africa
I
from
2023
have
attracted
worldwide
attention.
development
a
scalable
effective
vaccine
against
ongoing
epidemic
mpox
is
urgently
needed.
We
previously
constructed
two
bivalent
MPXV
mRNA
vaccines,
LBA
(B6R‐A29L)
LAM
(A35R‐M1R),
quadrivalent
vaccine,
LBAAM
(B6R‐A35R‐A29L‐M1R).
These
vaccines
at
20
µg
dose
could
induce
potential
antigen‐specific
immune
responses
provide
protection
lethal
VACV
challenge.
Compared
with
individual
LBA&
displayed
superior
protective
effects.
To
characterize
these
further,
we
monitored
long‐term
immunity
as
long
28
weeks
after
initial
immunization
optimized
dosages
to
decrease
cost
production
for
future
clinical
use.
Our
results
demonstrated
that
both
(A35R‐M1R)
tetravalent
elicit
long‐lasting
IgG
antibodies
well
neutralizing
MPXV.
They
all
provided
complete
challenge
until
post
prime
immunization.
Moreover,
immunogenicity
efficacy
(LBAAM
LAM)
are
dependent,
even
low‐dose
(1
µg)
sufficient
valuable
clues
further
use
humans.
Assessing
the
long-term
efficacy
of
MPXV
vaccine
candidates
is
crucial
for
global
response
to
ongoing
mpox
epidemic.
Built
upon
our
previous
study
quadrivalent
mRNA
vaccine,
herein
we
reported
that
MPXV-1103
could
elicit
sustained
humoral
and
cellular
immunity
in
mice,
including
induction
A35/B6/A29/M1-specific
IgG
antibodies,
VACV
neutralizing
antibodies
activated
cytotoxic
CD8+T
cells,
which
provides
100%
protection
against
lethal
challenge
even
at
280
days
after
first
vaccination.
Our
results
provide
critical
insights
orthopoxvirus
development.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Oct. 11, 2024
Monkeypox
(mpox)
is
a
zoonotic
illness
caused
by
the
monkeypox
virus
(MPXV),
with
higher
health
concerns
among
people
who
are
pregnant,
children,
and
persons
immunocompromised,
including
untreated
advanced
HIV
disease.
Significant
progress
has
been
made
in
developing
vaccines
against
mpox,
yet
critical
challenges
limitations
persist
ensuring
their
effectiveness,
safety,
accessibility.
The
pertinence
of
this
review
highlighted
World
Health
Organization's
declaration
global
emergency
on
August
14,
2024,
due
to
recent
mpox
outbreak,
underscoring
necessity
for
effective
vaccine
solutions
face
rapidly
evolving
virus.
Here,
we
comprehensively
analyze
various
platforms
utilized
prevention,
attenuated
non-replicating
vaccines,
viral
vector-based
recombinant
protein
DNA
mRNA
vaccines.
We
evaluate
advantages
each
platform,
highlighting
urgent
need
ongoing
research
innovation
enhance
efficacy
safety.
Recent
advancements,
such
as
incorporating
immunostimulatory
sequences,
improved
delivery
systems,
polyvalent
explored
potential
offer
broader
protection
diverse
orthopoxvirus
strains.
This
work
underscores
optimize
currently
available
investigate
novel
vaccination
strategies
address
future
public
emergencies
effectively.
By
focusing
these
methodologies,
aim
contribute
development
robust
adaptable
other
related
threats.
The
2022
global
mpox
virus
(MPXV)
outbreak
highlights
the
urgent
need
for
safer,
next-generation
vaccines.
We
compared
immunogenicity
and
protective
efficacy
of
individual
multicomponent
membrane
proteins
MPXV
virions
in
mice
to
inform
development
a
recombinant
subunit
vaccine
against
mpox.
BALB/c
were
immunized
with
eukaryotically
expressed
A35R,
A29L,
B6R,
M1R
proteins,
administered
individually
or
combinations
an
Al(OH)₃
+
CpG
oligodeoxynucleotide
adjuvant.
Three
protein
vaccines
(A29/B6,
A29/B6/M1,
A29/B6/M1/A35)
provided
complete
protection,
but
others
(individual
A35/M1
combinations)
partial
protection
challenge
high-lethal
doses
vaccinia
Western
Reserve
(VACV-WR).
Additionally,
A29/B6
conferred
whereas
A29/B6/M1
A29/B6/M1/A35
ectromelia
(ECTV),
being
most
effective.
All
induced
strong
antigen-specific
immunoglobulin
G
(IgG)
cellular
immunity,
only
four
(M1,
A35/M1,
exhibited
significant
neutralizing
activity
MPXV,
VACV-Tiantan,
ECTV.
Correlation
analysis
suggested
that
antibodies
A35-/A29-/B6-specific
immunity
act
as
complementary
defense
mechanisms,
potentially
providing
first-
second-line
related
orthopoxviruses.
Collectively,
demonstrated
best
efficacy.
This
study
provides
novel
insights
into
immunogen
optimization
potential
mechanisms
other
Frontiers in Pharmacology,
Journal Year:
2025,
Volume and Issue:
16
Published: April 28, 2025
The
mpox
disease,
caused
by
the
virus
(MPXV),
has
become
a
rising
public
health
issue
due
to
its
potential
cause
outbreaks.
Consistently,
this
investigation
aims
evaluate
current
advances
in
development
of
novel
immunotherapeutic
approaches
against
MPXV,
which
are
crucial
for
preventing
and
controlling
spread.
This
scoping
review
was
performed
analyzing
content
English-language
articles
published
between
2018
2024,
reported
next-generation
vaccines
MPXV
their
assessment
animal
models.
Patents
within
scope
research
were
also
included.
Contrarywise,
studies
based
solely
on
immunoinformatic
methods,
reviews,
book
chapters,
news,
others
excluded.
literature
search
executed
11
databases,
such
as
Scopus,
MEDLINE,
PubMed.
A
total
36
records
(32
4
patents)
included
review.
All
32
contain
preclinical
with
varied
group
sizes
(4-16)
main
models
BALB/c
mice.
Less
commonly
used
CAST/Ei
mice
cynomolgus
macaques.
Moreover,
most
targeted
one
or
more
antigens,
A29L,
A35R,
B6R,
M1R,
through
active
immunization
(via
mRNAs
recombinant
antigens)
passive
(antibody
delivery).
Overall,
new
generation
might
represent
prospective
candidates
combat
concern.
Nonetheless,
several
analyzed
possess
drawbacks,
including
limited
similarity
humans,
small
sizes,
brief
follow-up
durations.
Consequently,
additional
is
required
ascertain
long-term
protection,
efficacy,
safety
these
approaches.
Infectious Diseases of Poverty,
Journal Year:
2025,
Volume and Issue:
14(1)
Published: Feb. 25, 2025
Abstract
Background
The
monkeypox
virus
(MPXV)
has
raised
global
health
concerns
due
to
its
widespread
transmission.
This
study
evaluated
the
MPXV
immunogenic
antigens
and
impact
of
vaccinia
(VACV)
vaccination
infection
on
cross-reactive
antibody
responses
conserved
proteins
from
representative
strains
that
reflected
evolutionary
trajectory.
Methods
Phylogenetic
analyses
were
first
conducted
reveal
trajectory
1970
2024.
A
total
84
serum
samples
collected:
42
VACV-vaccinated
individuals,
12
MPXV-infected
participants
in
early
stage,
13
late
17
naive
individuals.
Demographic
data,
HIV
status,
as
well
other
clinical
information
collected
using
standardized
forms.
Immunogenicity,
responses,
amino
acid
similarity
15
surface
assessed
enzyme-linked
immunosorbent
assays,
VACV
neutralization
tests,
sequence
alignment.
Data
analysis
methods
included
variance,
Mann–Whitney
U
test,
binary
logistic
regression,
Pearson
correlation,
linear
with
a
significance
threshold
P
<
0.05.
Results
186
complete
genome
sequences
classified
into
different
clades
lineages,
ranging
clade
Ia
IIb
C.1.1.
Individuals
infected
demonstrated
strong
A35R,
B6R,
H3L,
E8L.
individuals
exhibited
broader
cross-reactivity,
particularly
against
A21L
(
=
0.0003),
A28L
0.0028),
A29L
0.0324),
G2R
H2R
0.0008),
compared
correlation
revealed
significant
associations
0.0049)
between
orthopoxviruses.
Furthermore,
greater
neutralizing
activity
than
those
0.0001),
while
vaccinated
group
retained
cross-protective
immunity
even
decades
post-vaccination.
Conclusions
E8L
are
main
MPXV.
VACV-vaccination
triggers
response
proteins.
Our
findings
suggest
need
for
targeted
vaccines
treatments
MPXV,
reintroduction
smallpox
vaccinations
booster
doses
high-risk
groups.
Graphical
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: March 26, 2025
The
persistent
monkeypox
outbreaks
intensify
the
demand
for
vaccines.
Based
on
mRNA
vaccine
platform,
we
conduct
a
systematic
screening
of
virus
(MPXV)
surface
proteins
from
two
types
viral
particles,
extracellular
enveloped
viruses
(EVs)
and
intracellular
mature
(MVs).
This
unveils
12
important
antigens
with
diverse
levels
neutralizing
immunogenicity.
Further
assessment
reveals
that
combinations
4,
8,
these
antigens,
namely
Mix-4,
Mix-8,
Mix-12,
induce
varying
degrees
immune
protection,
Mix-12
being
most
potent.
finding
demonstrates
significance
not
only
level
but
also
diversity
antibodies
in
providing
potent
protection.
Additionally,
utilize
T
cell-epitope
enrichment
strategy,
analyzing
complete
proteome
sequence
MPXV
to
predict
antigenic
epitope-rich
regions.
Integration
regions
into
cellular
immune-targeting
antigen,
named
MPX-EPs,
showcases
can
independently
confer
Furthermore,
co-immunization
MPX-EPs
achieves
protection
against
challenge.
Overall,
results
suggest
an
effective
approach
enhance
vaccines
through
specific
coordination
humoral
responses.
immunogenicity
screen
proteins,
authors
develop
which
they
combine
cell
achieve
coordinated
activation
